title: Virus-associated apoptosis of blood neutrophils as a risk factor for invasive meningococcal disease.
abstract: OBJECTIVE
  To quantify a range of haematological indicators of viral infection (leucocyte apoptosis, cytopenia of normal lymphocytes, reactive lymphocyte increase, neutropenia) in patients with recent onset invasive meningococcal disease (IMD), with a view to test the association of viral infection with IMD and identify possible haematological risk factors for its development.
  
  
  METHODS
  88 patients with recent onset IMD, classified on clinical severity as fatal (n=14), septic shock survived (n=26) and no shock (n=48), and 50 healthy controls were studied. Blood film microscopy and leucocyte counts were used to quantify the virus-associated indicators. Cocci-containing neutrophils were also quantified.
  
  
  RESULTS
  All viral parameters were significantly more frequent or higher in patients than controls, with leucocyte apoptosis found only in the patients. A significant gradient in accord with clinical severity was found for neutrophil and lymphocyte apoptosis, neutropenia and cocci-containing neutrophils. Crucially, apoptotic neutrophils did not contain cocci, and cocci-containing neutrophils were not apoptotic.
  
  
  CONCLUSIONS
  The correlation between magnitude of neutrophil apoptosis and severity of IMD suggests a cause-effect relationship. We propose that neutrophil apoptosis is more likely a facilitator rather than an effect of IMD for these reasons: (1) apoptotic neutrophils did not contain cocci and cocci-containing neutrophils were not apoptotic, (2) leucocyte apoptosis is a recognised viral effect and (3) Neisseria meningitidis is incapable of producing a Panton-Valentine type leucocidin. The lymphocyte apoptosis which accompanies neutrophil death may contribute to risk by impairing the generation of microbicidal antibody. Leucocyte apoptosis is a morphological expression of viral immunosuppression and, we suggest, is a likely contributor to a range of viral effects.
authors.affiliation: Department of Paediatrics, University of Queensland, Royal Children's Hospital, , Brisbane, Queensland, Australia.
authors.forename: Harry
authors.initials: H
authors.lastname: Smith
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Rogers
authors.forename: Helen V
authors.initials: HV
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Gillis
authors.forename: Victor
authors.initials: V
authors.lastname: Siskind
authors.forename: Judith A
authors.initials: JA
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology; D008589:Meningococcal Infections / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000276:immunology*; D009503:Neutropenia / Q000276:immunology / Q000473:pathology*; D009504:Neutrophils / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D012307:Risk Factors; D014777:Virus Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor
keywords: Apoptosis; Leucocytes; Virus